Ryaby James T, Sheller Michael R, Levine Benjamin P, Bramlet Dale G, Ladd Amy L, Carney Darrell H
OrthoLogic Corp, 1275 West Washington Street, Tempe, AZ 85281, USA.
J Bone Joint Surg Am. 2006 Nov;88 Suppl 3:132-9. doi: 10.2106/JBJS.F.00892.
The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-three-amino-acid peptide that represents a portion of the receptor-binding domain of the native human thrombin molecule that has been identified as the binding site for a specific class of receptors on fibroblasts and other cells. Preclinical studies with this peptide have shown that it can accelerate tissue repair in both soft and hard tissues by mechanisms that appear to involve up-regulation of genes that initiate a cascade of healing events. These events include recruitment and activation of inflammatory cells, directed migration of cells (chemotaxis), cell proliferation, elaboration of extra-cellular matrix, and accelerated revascularization of the healing tissues. Early preclinical dermal wound-healing studies showed that TP508 accelerated healing of both incisional wounds and full-thickness excisional wounds in normal and ischemic skin. In all of these studies, the accelerated healing was associated with increased neovascularization across the incision or in the granulating wound bed. Studies in a rat fracture model have also shown that TP508 accelerates the rate of fracture repair. Gene array analysis of fracture callus from control and TP508-treated fractures indicated that TP508 treatment was associated with an up-regulation of early response elements, inflammatory mediators, and genes related to angiogenesis. Similar to what had been seen in dermal wounds, histology from rat fracture callus twenty-one days after treatment indicated that fractures treated with TP508 had significantly more large functional blood vessels than did fractures in the control animals. In vitro studies support these in vivo data and indicate that TP508 may have a direct angiogenic effect by promoting the rate of new vessel growth. The results from phase-1 and phase-2 human clinical studies have shown a positive stimulatory effect of TP508 in the healing of diabetic ulcers and in the repair of fractures to the distal aspect of the radius. Collectively, these studies suggest that TP508 accelerates tissue repair by initiating a cascade of events that lead to an increased rate of tissue revascularization and regeneration.
凝血酶肽TP508，也被称为Chrysalin（美国亚利桑那州坦佩市的OrthoLogic公司），是一种由23个氨基酸组成的肽，它代表天然人凝血酶分子受体结合域的一部分，该结合域已被确定为成纤维细胞和其他细胞上特定类型受体的结合位点。对该肽的临床前研究表明，它可以通过上调启动一系列愈合事件的基因的机制，加速软组织和硬组织的修复。这些事件包括炎症细胞的募集和激活、细胞的定向迁移（趋化作用）、细胞增殖、细胞外基质的形成以及愈合组织的血管再生加速。早期的临床前皮肤伤口愈合研究表明，TP508可加速正常皮肤和缺血皮肤的切开伤口和全层切除伤口的愈合。在所有这些研究中，愈合加速与切口或肉芽创面床的新血管形成增加有关。大鼠骨折模型的研究也表明，TP508可加速骨折修复。对对照组和TP508治疗组骨折骨痂的基因阵列分析表明，TP508治疗与早期反应元件、炎症介质以及与血管生成相关基因的上调有关。与皮肤伤口中观察到的情况类似，治疗21天后大鼠骨折骨痂的组织学检查表明，TP508治疗的骨折比对照动物的骨折有明显更多的大功能性血管。体外研究支持这些体内数据，并表明TP508可能通过促进新血管生长速率而具有直接的血管生成作用。1期和2期人体临床研究结果表明，TP508对糖尿病溃疡的愈合以及桡骨远端骨折的修复具有积极的刺激作用。总体而言，这些研究表明，TP508通过启动一系列导致组织血管再生和再生速率增加的事件来加速组织修复。
